title: Subcutaneous cholera toxin exposure induces potent CD103⁺ dermal dendritic cell activation and migration.
abstract: CD103⁺ dermal dendritic cells (dDCs) are a recently described DC subset of the skin shown to be the principal migratory DCs capable of efficiently cross-presenting antigens and activating CD8⁺ T cells. Harnessing their activity would promote vaccine efficacy, but it has been unclear how this can be achieved. We tested a panel of adjuvants for their ability to affect dDCs. In comparison to the other adjuvants tested, the capacity of cholera toxin (CT) to induce the migration of dDCs was unique. Within 24 h of CT injection, large numbers of highly activated dDCs (including CD103⁺ dDCs) migrated to the draining lymph nodes and cross-presented coinjected antigens, potently activating naïve CD8⁺ T cells. Peptide vaccines adjuvanted with CT induced T-cell responses uniquely characterized by dynamic cytokine responses including the production of IL-2, and such vaccines were protective in situations reliant on CD8⁺ T-cell responses, including liver-stage Plasmodium challenge, or tumor challenge. This study is the first to examine the effects of adjuvants on CD103⁺ dDCs and identifies CT as a prototypical adjuvant for the activation of CD103⁺ dDCs, opening the way to development of vaccines and adjuvants that specifically target dDCs and generate effective CD8⁺ T-cell responses.
authors.affiliation: Queensland Institute of Medical Research, Queensland Tropical Health Alliance and Australian Centre for Vaccine Development, Royal Brisbane Hospital, Brisbane, Australia.
authors.forename: Simon H
authors.initials: SH
authors.lastname: Apte
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Redmond
authors.forename: Penny L
authors.initials: PL
authors.lastname: Groves
authors.forename: Sophie
authors.initials: S
authors.lastname: Schussek
authors.forename: David J
authors.initials: DJ
authors.lastname: Pattinson
authors.forename: Denise L
authors.initials: DL
authors.lastname: Doolan
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000276:immunology*; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000008:administration & dosage / Q000276:immunology*; D045142:Cross-Priming / Q000187:drug effects; D006801:Humans; D007279:Injections, Subcutaneous; D039001:Integrin alpha Chains / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D010961:Plasmodium / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D039001:Integrin alpha Chains; D022223:Vaccines, Subunit; C091367:alpha E integrins; D002772:Cholera Toxin
keywords: Adjuvants; CD8+ T cells; Cholera toxin; DCs; Vaccines